Atividade antiplasmodial e modelagem molecular de novas chalconas e derivados

Abstract

Malaria is an infection caused by Plasmodium sp. and It can be serious, if not treated precociously. It affects significant fraction of humanity and has profound health impact worldwide. It is estimated that 3.3 billion people are exposed to the risk of transmission. One of the problems of the infection is the growing emergence of parasite resistance to antimalarial drugs. In this context, studies are needed to develop new alternative chemotherapy. Many substances, such as the chalcones, have had their antiplasmodial activity proven. However, the physicochemical properties of these molecules, which are important for biological actions, are not well established. In this work, molecular modeling was performed and the antiplasmodial activity was evaluated of two chalcones (HBR1, and LH2) and four derivatives of chalcones (GH3, IV4, LCH1, and LCH3). For that, we determined the drug concentration inhibitory of 50% of the growth of P. falciparum in vitro as well as the physicochemical properties of derivatives of chalcones as HOMO, LUMO, electrostatic potential, C log P, hydration energy, polarizability and molecular volume through virtual calculations. The results of the calculated values were correlated with the biological activity in order to identify chemical parameters that can influence the antiplasmodial action. The inhibitory concentrations in 50% of the growth of P. falciparum ranged from 0,2 to 1,7 M, and these values were smaller than described them in the literature. The study of the correlation between the biological activities and the physicochemical properties showed determinating parameters for the biological activity, as LUMO, electrostatic potential, C log P and hydration energy, which may help in the selection of molecules more active against P. falciparum. Thus, these molecular properties can be used in the rational planning of new chalcones and/or derivatives with antiplasmodial activity.